Approximately 100,000 adolescents and young adults in the
United States experience a first episode of psychosis (FEP) every year. The
early phase of psychotic illness is widely viewed as a critical opportunity
for indicated prevention, and a chance to alter the downward trajectory and
poor outcomes associated with schizophrenia and related psychotic disorders.
Compared to traditional treatment approaches, programs that integrate
pharmacologic, psychological, and rehabilitation interventions for FEP, i.e.,
team-based Coordinated Specialty Care (CSC), have been found to produce a
range of positive clinical and functional outcomes. However, the timing of
treatment is critical; short and long-term outcomes are better when
individuals begin treatment close to the onset of psychosis. Unfortunately, numerous
studies find a substantial delay between the onset of psychotic symptoms and
the initiation of FEP care; in the U.S. treatment is typically delayed
between one and three years. Early identification of FEP, rapid referral to
evidence-based services, and effective engagement in CSC are essential to
shortening the duration of untreated psychosis (DUP) and pre-empting the
functional deterioration common in psychotic disorders. The World Health
Organization advocates reducing DUP to 3 months or less. Accordingly, this
Funding Opportunity Announcement (FOA) seeks research project grant
applications that test practical, reproducible strategies for substantially
reducing DUP among persons with FEP by eliminating bottlenecks or closing
gaps in the pathway to CSC services.

Key Dates

Posted Date

May 17, 2016

Open Date (Earliest Submission Date)

June 19, 2016

Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

Any due dates on or after Jan 25, 2018 must use reissued FOA.

July 19, 2016; November 18, 2016; March 17, 2017; July 18,
2017; November 17, 2017; March 19, 2018; July 18, 2018; November 19, 2018;
March 19, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed
for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

November 2016, March 2017, June 2017, November 2017, March
2018, June 2018, November 2018, March 2019, June,2019

Advisory Council Review

January 2017, May 2017, October r 2017, January 2018, May
2018, October 2018, January 2019, May 2019, October 2019

Earliest Start Date

April 2017, July 2017, September 2017, April 2018. July
2018, September 2018, April 2019, July 2019, September 2019

Expiration Date

New Date January 24, 2018 per reissuance of FOA (Original Expiration Date: March 20, 2019)

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH
Guide for Grants and Contracts). Conformance to all requirements (both
in the Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

Approximately 100,000 adolescents and young adults in the
United States experience a first episode of psychosis (FEP) every year. The
early phase of psychotic illness is widely viewed as a critical opportunity for
indicated prevention, and a chance to alter the downward trajectory and poor
outcomes associated with schizophrenia and related psychotic disorders.
Compared to traditional treatment approaches, programs that integrate
pharmacologic, psychological, and rehabilitation interventions for FEP, i.e.,
team-based Coordinated Specialty care (CSC), have been found to produce a range
of positive clinical and functional outcomes, including reduced symptoms,
greater involvement in work or school, and improved quality of life. However,
the timing of treatment is critical; short and long-term outcomes are better
when individuals begin treatment close to the onset of psychosis.

International consensus statements from the World Health
Organization recommend that specialty care for FEP start within 3 months of
illness onset. However, more than two dozen studies conducted worldwide have
observed a substantial delay (on average 2 years) between the appearance of
psychotic symptoms and the initiation of treatment. Two influential
meta-analyses clearly establish that the duration of untreated psychosis (DUP),
the time between the onset of psychosis and initiation of treatment, is
correlated with poor outcome. In the United States, DUP ranges between one and
three years, suggesting that many people with FEP are missing a critical
opportunity to benefit from early psychosis intervention.

Research suggests that DUP can be reduced by enhancing early
detection, treatment referral, and clinical engagement mechanisms. Reducing DUP
in the United States from current levels of 1-3 years to the international
standard of no more than 3 months should be a major focus of applied research
efforts. Research to improve FEP case identification and referral in the United
States is a logical complement to other NIMH initiatives on improving outcomes
for people with FEP, such as the Recovery
After an Initial Schizophrenia Episode (RAISE)l initiative, which found that
CSC produced superior clinical and functional improvements compared to typical
care, especially among clients with shorter DUP.

Research Objectives

This FOA aims to support research that will test feasible
and reproducible strategies for substantially reducing DUP among persons with
FEP seeking care in U.S. community treatment settings. The research may focus
on eliminating bottlenecks or closing gaps in the pathway to specialty FEP
care. For the purpose of this announcement, we define "bottlenecks"
and “gaps” as individual, organizational, systemic, or other impediments to
rapid FEP identification, assessment, connection to and engagement in specialty
FEP care. The target population is not limited to first episode schizophrenia,
but includes all persons experiencing a first episode of psychosis regardless
of presenting DSM-IV diagnosis. Applicants are encouraged to base research
activities in settings that link to treatment systems with CSC programs for
FEP. A variety of configurations for FEP specialty care programs are possible,
but evidence-based CSC treatment involves integrated, team-based care and
typically features use of single antipsychotic medications, prescribed in low
doses; family psychoeducation; supported employment and/or education;
cognitive-behavioral therapy oriented to recovery; coordination with primary
care services; and continuity of care across inpatient and outpatient treatment
settings.

Applications submitted to this FOA should propose projects
that test practical approaches for producing one or more of the following:

Methods to achieve expeditious referral of persons with FEP, or
those at high clinical risk of psychosis, to an appropriate specialty care
treatment program; and

Strategies for achieving rapid engagement and initiation of FEP
treatment.

The strategies proposed to reduce DUP should aim to close
gaps as well as remove significant bottlenecks in the referral pathway to CSC,
including barriers that impede the following:

Recognition of psychotic symptoms

Referral to mental health treatment

Diagnosis of a psychotic disorder

Referral to a CSC program

Enrollment in a CSC program and/or initiation of CSC treatment

Engagement in CSC services

Applications submitted to this FOA should consider “supply
side” approaches (e.g., targeting clinical and community systems), such as the
development and testing of strategies for training primary care physicians and
nurses, school and college counselors, emergency department staff, police, and
mental health “generalists” to recognize signs of early psychosis, and the
improvement of referral networks to fast-track the initiation of FEP care. This
FOA is also intended to encourage “demand side” approaches (e.g., engaging
people with FEP and their family members, friends, caregivers and others close
to the affected individual) to improve recognition of early symptoms,
help-seeking, access, and engagement in care for persons with FEP and/or youth
at high clinical risk for psychosis, through education, decision-support
systems, and other tools, including social marketing, social media and social
networking.

Research to reduce DUP requires expertise on the
characteristics of service delivery systems and community settings in which DUP
reduction strategies would be embedded, as well as expertise on the needs, life
circumstances, and diversity of the population of young people with FEP and/or
at high clinical risk of psychosis. Investigators should convey knowledge of
DUP assessment strategies and factors that may contribute to treatment delays
in the U.S. health care system. Multi-disciplinary research teams with
complementary areas of expertise are encouraged. NIMH also encourages
applications that involve collaboration with stakeholders from multiple
clinical or community practice settings, as well as consumers of services and
their family members and social contacts.

In addition, NIMH welcomes applications proposing to
leverage existing practice research infrastructures such as the Mental Health
Research Network (MHRN), the Clinical Translational Science Awards Program
(CTSA) and other research and practice networks looking to conduct studies to
reduce DUP. NIMH also welcomes coordination of DUP reduction research with
other public and private initiatives that specifically address early
identification and treatment of young people at high risk for mental illness.
For example, since 2014 the Substance Abuse and Mental Health Services
Administration (SAMHSA) has supported the implementation of evidence-based
treatment programs for FEP across the United States via a set-aside in the
Community Mental Health Block Grant Program (CMHBG). The NIMH estimates that by
2017, over 100 CSC programs will be operating in 32 states, as a consequence of
the CMHBG set-aside, representing a tremendous opportunity for advancing DUP
reduction research.

This FOA, and the related FOA, PAR-16-264,
support experimental and quasi-experimental studies focused on designing,
refining, and testing algorithms of practical and accurate case identification
of persons with FEP and/or at high risk of psychosis within a myriad of
possible clinical and community contexts, in combination with strategies that
promote rapid referral to the appropriate stage-specific specialty care.

ResearchTopics

Applications to this FOA should focus on practical and
reproducible strategies to achieve substantial DUP reduction for persons with
FEP. The NIMH encourages applications in which referral to CSC programs is
feasible. This FOA supports studies on the research topics listed below, which
are intended to be illustrative, not exhaustive:

Testing the effectiveness of strategies to improve identification
and referral of patients with FEP within emergency service systems to
appropriate stage-specific care.

Improving case identification and referral of patients with FEP
within non-specialty clinical and community systems (e.g., primary care, high
schools, criminal justice settings, college campuses, or workplace).

Improving access and engagement in care of persons in the
high-risk state for psychosis, resulting in rapid FEP identification and entry
into specialty FEP care.

Improving recognition of symptoms and increasing help-seeking
behavior among people with FEP and those at high risk of psychosis.

Improving recognition of symptoms and increasing help-seeking
behavior among people with FEP who often experience the highest levels of
health disparities, including members of racial or ethnic minority groups or
persons who identify as lesbian, gay, bisexual or transgender.

Improving recognition of early psychosis symptoms among family
members and friends of persons with FEP, and facilitating their help-seeking
and supportive behaviors on behalf of individuals with FEP.

Developing and testing decision-support tools, including those
embedded in electronic health records, for improving the early identification
of FEP and matching of symptomatic and functional deficits with available
service systems within a catchment area.

Assessing the impact of high risk of psychosis/FEP public
awareness campaigns on initiation of treatment and DUP.

Social marketing, social media, and social networking approaches
to identify persons at high risk of psychosis or with FEP and link to
treatment.

It is expected that applications submitted to this FOA will
identify other important, innovative and impactful research topics.
Investigators considering applying to this FOA are encouraged to contact the Scientific/Research Contact for this FOA for additional
guidance prior to submitting an application.

A variety of rigorous methodological approaches are possible
for testing the impact of the proposed approach to reducing DUP. These
approaches include randomized controlled trials, quasi-experimental designs
with non-randomized comparison groups, time series designs, and other designs
of equivalent rigor and relevance. Considerations for selecting a research
design for the proposed study include the scientific question that the study is
designed to answer, practical constraints, ethical issues, and the tradeoff
between maximizing internal and external validity.

Investigators in this area whose work is at a developmental
stage should consider applying to the companion FOA, PAR-16-264.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible
to apply.
Foreign components, as defined in
the NIH Grants Policy Statement, are allowed.

Required
Registrations

Applicant
Organizations

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either create
a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing Official,
they must have two distinct eRA Commons accounts, one for each role. Obtaining
an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping
applications under review at the same time. This means that the NIH will
not accept:

A new (A0) application that is submitted before issuance of the
summary statement from the review of an overlapping new (A0) or resubmission
(A1) application.

A resubmission (A1) application that is submitted before issuance
of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another
application pending appeal of initial peer review (see NOT-OD-11-101).

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must obtain the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, including Supplemental
Grant Application Instructions except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must
be followed.

Biographical
Sketch

Describe investigators' knowledge of DUP assessment
strategies and factors that may contribute to treatment delays in the U.S.
health care system. The biographical sketches should also describe the
qualifications of the PD/PI and other senior investigators, including expertise
in the identification and treatment of people with FEP and expertise in the
service delivery systems or community settings in which the selected DUP
reduction strategies would be embedded.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Research
Strategy: As part of the research strategy, applications should
present empirical data that support the feasibility and acceptability of the
proposed strategy for reducing DUP. The empirical data presented for the
selected setting should (1) quantify the overall DUP among persons with FEP at
baseline using a scientifically acceptable operational definition of DUP and
reliable measures of DUP, (2) map the various referral pathways that channel
persons with FEP to FEP specialty care programs, and (3) identify gaps and
bottlenecks in these referral pathways that prolong DUP.

Applications should propose a DUP reduction approach that
has the potential to substantially reduce DUP in the target population of
people with FEP. Applications should also describe novel strategies proposed
for reducing DUP among people with FEP and/or measuring DUP in community
treatment settings in the U.S. The application should describe a project that
involves substantial DUP reduction for persons with FEP as a primary outcome.

The application should provide justification for the sample
size in terms of feasibility goals and present a clear rationale for the choice
of methods proposed, explaining how the selected research methods minimize
confounds that may limit the ability to infer causality. Regardless of the
proposed methods, the project should include assessment of DUP.

Applications should describe appropriate study milestones
that are clearly defined for all of the study aims. The milestones should be
feasible and quantifiable and described in the context of the study timeline.
Potential challenges that may result in enrollment shortfalls should be
discussed, along with and corresponding solutions to address enrollment
problems.

Applications should describe the multi-disciplinary features
of the proposed research team, including team members' complementary areas of
expertise.

The application should also describe collaborations with
stakeholders from multiple clinical or community practice settings, as well as
with consumers of services and their family members and social contacts,
detailing stakeholders' engagement in the research process, including project
design.

For
projects involving a clinical trial:

Applications should identify the target(s) of the proposed
services intervention to reduce DUP and provide evidence of the association
between those targets and the outcomes of interest (e.g., DUP, symptoms,
functioning). The application should also provide evidence that: 1) the
outcome measures have been validated, 2) the outcomes measured include
stakeholder relevant outcomes, 3) the intervention could be implemented in
typical service settings using typically available personnel and resources, and
4) fidelity in intervention delivery will be monitored. Include the
following:

(1) a conceptual framework that clearly identifies the
target(s)/mechanism(s) and the empirical evidence linking the
target(s)/mechanism(s) to the reduction in DUP;

(2) plans for assessing whether the services intervention
engages the target(s)/mechanism(s) using valid measures that are as direct and
objective as is feasible, including the specific measures, the assessment
schedule, and the justification for the assessment strategy (e.g., evidence
regarding the validity and feasibility of the proposed measures);

(3) an analytic strategy and corresponding power calculations
for data analyses that will be used to examine whether the intervention engages
the target(s) and whether intervention-induced changes in the target(s) are
associated with reduction in DUP (i.e., mediation).

(4) justification for the sample size; and

(5) a rationale for the choice of methods, including how the
selected methods minimize confounds that may limit ability to infer causality.

In the case of multi-element interventions, the application
should specify the conceptual basis, assessment plan, and analytic strategy, as
detailed above, for the target(s)/mechanism(s) corresponding to each DUP
reduction intervention element.

The NIMH has published updated policies and guidance for
investigators regarding human research protection and clinical research data
and safety monitoring (NOT-MH-15-025).
The application’s Protection of Human Subjects section should reflect the
policies and guidance in this notice. Plans for the protection of
research subjects and data and safety monitoring will be reviewed by the NIMH
for consistency with NIMH and NIH policies and federal regulations.

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans as provided in the SF424 (R&R)
Application Guide, with the following modification:

To advance the goal of further research through widespread
data sharing among researchers, investigators funded under this FOA are
expected to share those data via the NIMH Data Archive (NDA) (https://ndar.nih.gov/; see NOT-MH-09-005, NOT-MH-14-015 and NOT-MH-15-012). Established by the NIH, the NDA is a secure
informatics platform for scientific collaboration and data-sharing that enables
the advancement of research through the effective communication of detailed
research results, tools, and supporting documentation.

Investigators funded under this FOA are expected to use NDA
technologies to submit data in accordance with the NDA Data Sharing Terms and
Conditions, incorporated by reference, which can be found at https://ndar.nih.gov/contribute_data_sharing_regimen.html.
The resource sharing plan should be formulated in accordance with the NDA Data
Sharing Terms and Conditions.

Appendix:
Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

PHS Inclusion Enrollment Report

When conducting clinical research, follow all instructions
for completing PHS Inclusion Enrollment Report as described in the SF424
(R&R) Application Guide.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide
must be followed.

3. Unique Entity Identifier
and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the
requirement for obtaining a unique entity identifier and for completing and
maintaining active registrations in System for Award Management (SAM), NATO
Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and
Grants.gov

4. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to
submit applications before the due date to ensure they have time to make any
application corrections that might be necessary for successful submission. When
a submission date falls on a weekend or Federal
holiday, the application deadline is automatically extended to the next
business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date and time. If a Changed/Corrected application is submitted after the
deadline, the application will be considered late. Applications that miss the
due date and time are subjected to the NIH Policy on Late Application
Submission.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically. If you encounter a system issue beyond your control that
threatens your ability to complete the submission process on-time, you must
follow the Guidelines
for Applicants Experiencing System Issues. For assistance with application
submission, contact the Application Submission Contacts in Section VII.

Important
reminders:

All PD(s)/PI(s) must include their eRA Commons ID in
the Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS
number it provides on the application is the same number used in the
organization’s profile in the eRA Commons and for the System for Award Management.
Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for completeness
and compliance with application instructions by the Center for Scientific
Review, NIH. Applications that are incomplete or non-compliant will not be
reviewed.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in
any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application
and follow the Policy on the Acceptance for Review of Unsolicited Applications
that Request $500,000 or More in Direct Costs as described in the SF424
(R&R) Application Guide.

Use of Common Data Elements in NIH-funded Research

NIMH encourages the use of common data elements (CDEs) in
basic, clinical, and applied research, patient registries, and other human
subject research to facilitate broader and more effective use of data and
advance research across studies. CDEs are data elements that have been
identified and defined for use in multiple data sets across different
studies. Use of CDEs can facilitate data sharing and standardization to
improve data quality and enable data integration from multiple studies and
sources, including electronic health records. NIH ICs have identified
CDEs for many clinical domains (e.g., mental illness), types of studies (e.g.
genome-wide association studies (GWAS)), types of outcomes (e.g.,
patient-reported outcomes), and patient registries (e.g., the Global Rare
Diseases Patient Registry and Data Repository). NIH has established a
“Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to
assist investigators in identifying NIH-supported CDEs when developing
protocols, case report forms, and other instruments for data collection.
The Portal provides guidance about and access to NIH-supported CDE initiatives
and other tools and resources for the appropriate use of CDEs and data
standards in NIH-funded research. Investigators are encouraged to consult
the Portal, in particular the Consensus Measures for Phenotypes and eXposures
Mental Health Research Toolkit (https://www.phenxtoolkit.org/),
and describe in their applications any use they will make of NIH-supported CDEs
in their projects.

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an
important problem or a critical barrier to progress in the field? Is there a
strong scientific premise for the project? If the aims of the project are achieved,
how will scientific knowledge, technical capability, and/or clinical practice
be improved? How will successful completion of the aims change the concepts,
methods, technologies, treatments, services, or preventative interventions that
drive this field? Does the proposed approach have the potential to
substantially reduce DUP in the target population of people with FEP?

Investigator(s)

Are the PD(s)/PI(s), collaborators,
and other researchers well suited to the project? If Early Stage Investigators
or
those in the early stages
of independent careers, do they
have appropriate experience and training? If established, have they
demonstrated an ongoing record of accomplishments that have advanced their
field(s)? If the project is collaborative or multi-PD/PI, do the investigators
have complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project? Do the
qualifications of the PD/PI and other senior investigators include expertise in
the identification and treatment of people with FEP and expertise in the
service delivery systems or community settings in which the selected DUP
reduction strategies would be embedded? Do research team members have
complementary areas of expertise?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed? Are novel
strategies proposed for reducing DUP among people with FEP and/or measuring DUP
in community treatment settings in the U.S.?

Approach

Are the overall strategy,
methodology, and analyses well-reasoned and appropriate to accomplish the specific
aims of the project? Have the investigators presented strategies to ensure a
robust and unbiased approach, as appropriate for the work proposed? Are
potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed? Have
the investigators presented adequate plans to address relevant biological
variables, such as sex, for studies in vertebrate animals or human subjects?
Does the application present empirical data that support the feasibility and
acceptability of the proposed strategy for reducing DUP?

Does the project include a scientifically acceptable
operational definition of DUP? Are methods described for obtaining reliable
estimates of DUP in community programs? Does the project include substantial
DUP reduction for persons with FEP as a primary outcome? If clinical, community
or public health settings are involved, are stakeholders sufficiently engaged
in the research process, including project design?

For projects involving a clinical trial, does the
application provide evidence of the association between the intervention
target(s) and the endpoint(s) of interest? Are the outcome measures validated
and are stakeholder relevant outcomes included? Does the application describe
the monitoring of fidelity in intervention delivery in community practice
settings? Does the application provide justification for the sample size? Is
there a clear rationale for the choice of methods proposed? Does the application
explain how the selected research methods minimize confounds that may limit the
ability to infer causality?

Does the project involve
collaborations with relevant stakeholders? If the project involves human
subjects and/or NIH-defined clinical research, are the plans to address 1) the
protection of human subjects from research risks, and 2) inclusion (or
exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as
well as the inclusion or exclusion of children, justified in terms of the
scientific goals and research strategy proposed?

Does the application describe
appropriate milestones that are clearly defined for all of the study aims?

Environment

Will the scientific environment in
which the work will be done contribute to the probability of success? Are the
institutional support, equipment and other physical resources available to the
investigators adequate for the project proposed? Will the project benefit from
unique features of the scientific environment, subject populations, or
collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and technical
merit, and in providing an overall impact score, but will not give separate
scores for these items.

Protections for Human Subjects

For research that involves human
subjects but does not involve one of the six categories of research that are
exempt under 45 CFR Part 46, the committee will evaluate the justification for
involvement of human subjects and the proposed protections from research risk
relating to their participation according to the following five review
criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3)
potential benefits to the subjects and others, 4) importance of the knowledge
to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human
subjects and meets the criteria for one or more of the six categories of
research that are exempt under 45 CFR Part 46, the committee will evaluate: 1)
the justification for the exemption, 2) human subjects involvement and
characteristics, and 3) sources of materials. For additional information on
review of the Human Subjects section, please refer to the Guidelines for the Review of Human
Subjects.

Inclusion of Women, Minorities,
and Children

When the proposed project involves
human subjects and/or NIH-defined clinical research, the committee will
evaluate the proposed plans for the inclusion (or exclusion) of individuals on
the basis of sex/gender, race, and ethnicity, as well as the inclusion (or
exclusion) of children to determine if it is justified in terms of the
scientific goals and research strategy proposed. For additional information on
review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion
in Clinical Research.

Vertebrate Animals

The committee will evaluate the
involvement of live vertebrate animals as part of the scientific assessment
according to the following criteria: (1) description of proposed procedures
involving animals, including species, strains, ages, sex, and total number to
be used; (2) justifications for the use of animals versus alternative models
and for the appropriateness of the species proposed; (3) interventions to
minimize discomfort, distress, pain and injury; and (4) justification for
euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia
of Animals. Reviewers will assess the use of chimpanzees as they would any
other application proposing the use of vertebrate animals. For additional
information on review of the Vertebrate Animals section, please refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether
materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Resubmissions

For Resubmissions, the committee
will evaluate the application as now presented, taking into consideration the
responses to comments from the previous scientific review group and changes
made to the project.

Renewals

For Renewals, the committee will
consider the progress made in the last funding period.

Revisions

For Revisions, the committee will
consider the appropriateness of the proposed expansion of the scope of the
project. If the Revision application relates to a specific line of
investigation presented in the original application that was not recommended
for approval by the committee, then the committee will consider whether the
responses to comments from the previous scientific review group are adequate
and whether substantial changes are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Not Applicable

Select Agent Research

Reviewers will assess the
information provided in this section of the application, including 1) the
Select Agent(s) to be used in the proposed research, 2) the registration status
of all entities where Select Agent(s) will be used, 3) the procedures that will
be used to monitor possession use and transfer of Select Agent(s), and 4) plans
for appropriate biosafety, biocontainment, and security of the Select Agent(s).

For projects involving key biological and/or chemical resources,
reviewers will comment on the brief plans proposed for identifying and ensuring
the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the
budget and the requested period of support are fully justified and reasonable
in relation to the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by NIMH, in
accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Applications will be assigned to the appropriate NIH
Institute or Center. Applications will compete for available funds with all
other recommended applications . Following initial peer review, recommended applications
will receive a second level of review by the National Advisory Mental Health
Council. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons. Refer to Part 1 for dates for peer review, advisory council
review, and earliest start date.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA)
will be provided to the applicant organization for successful applications. The
NoA signed by the grants management officer is the authorizing document and
will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described
in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be
subject to terms and conditions found on the Award
Conditions and Information for NIH Grants website. This includes any
recent legislation and policy applicable to awards that is highlighted on this
website.

Recipients of federal financial
assistance (FFA) from HHS must administer their programs in compliance with
federal civil rights law. This means that recipients of HHS funds must ensure
equal access to their programs without regard to a person’s race, color,
national origin, disability, age and, in some circumstances, sex and religion.
This includes ensuring your programs are accessible to persons with limited
English proficiency. HHS recognizes that research projects are often limited
in scope for many reasons that are nondiscriminatory, such as the principal
investigator’s scientific interest, funding limitations, recruitment
requirements, and other considerations. Thus, criteria in research protocols
that target or exclude certain populations are warranted where
nondiscriminatory justifications establish that such criteria are appropriate
with respect to the health or safety of the subjects, the scientific study
design, or the purpose of the research.

For additional guidance regarding how the provisions apply
to NIH grant programs, please contact the Scientific/Research Contact that is
identified in Section VII under Agency Contacts of this FOA. HHS provides
general guidance to recipients of FFA on meeting their legal obligation to take
reasonable steps to provide meaningful access to their programs by persons with
limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html.
The HHS Office for Civil Rights also provides guidance on complying with civil
rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html;
and http://www.hhs.gov/ocr/civilrights/understanding/index.html.
Recipients of FFA also have specific legal obligations for serving qualified
individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
Please contact the HHS Office for Civil Rights for more information about
obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS
Departmental goal to ensure access to quality, culturally competent care,
including long-term services and supports, for vulnerable populations. For
further guidance on providing culturally and linguistically appropriate
services, recipients should review the National Standards for Culturally and
Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH
Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants to
report information about first-tier subawards and executive compensation under
Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.